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Recombinant expression of functional biological molecules and particularly full length membrane proteins for the biotechnology, medical and allied health industry is a challenging endeavour.
Membrane proteins constitute attractive targets for biotechnological applications such as diagnostic, biosensors, stem cell culture and tissue repair and vaccine. However these proteins are extremely difficult to produce compared to their soluble counterparts. The process generally involves detergent solubilisation with the risk of inactivating the protein by denaturation, an increased cost and often incompatibilities with downstream applications. The solution commonly adopted is to express only the soluble portion of the protein of interest but this results in an artificial construct that potentially misses some of the characteristics of the full-length native protein.
Despite much progress in understanding the mechanisms of immunity, vaccines against major pathogens, such as without limitation HIV and Plasmodium spp. remain elusive. In recent years, alternative antigen delivery systems have been actively investigated for greater efficacy, safety and ease of production. The most successful of these approaches has been virus-like particles (VLP) relying on self-assembly of viral structural proteins (HBV, papillomavirus). However, many pathogens do not produce such assemblies and there are limitations to the size of the antigens that can be incorporated into VLP scaffolds. The administration of antigens as particles is thought to have a number of advantages. Antigen presenting cells take up particulate antigens preferentially and traffic them to cellular compartments facilitating the production of antibody and cellular responses (see review by Rice-Ficht et al., Current Opinion in Microbiology, 13: 106-112, 2010).
There remains a need for a versatile platform technology able to provide stable and functional proteins, including membrane proteins, for myriad applications.